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Volume 31, Number 12—December 2025

CME ACTIVITY - Research

Pregnancy Outcomes after Exposure to Tuberculosis Treatment in Phase 3 Clinical Trial, 2016–2020

Ekaterina V. KurbatovaComments to Author , William C. Whitworth, Kia E. Bryant, Meredith G. Dixon, Kelly E. Dooley, Nigel A. Scott, Rosanna Boyd, Nicole E. Brown, Kimberley N. Chapman Hedges, Wendy Carr, Lakshmi P. Peddareddy, Grace Muzanyi, Rodney Dawson, Ziyad Waja, Neil Martinson, Jyoti S.V. Mathad, Payam Nahid, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, Patrick P.J. Phillips, and AIDS Clinical Trials Group A5349,1 and Tuberculosis Trials Consortium Study 312
Author affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (E.V. Kurbatova, W.C. Whitworth, K.E. Bryant, M.G. Dixon, N.A. Scott, R. Boyd, N.E. Brown, K.N. Chapman Hedges, W. Carr, L.P Peddareddy); Vanderbilt University Medical Center, Nashville, Tennessee, USA (K.E. Dooley); Uganda–Case Western Reserve University Research Collaboration, Kampala, Uganda (G. Muzanyi); University of Cape Town Lung Institute, Cape Town, South Africa (R. Dawson); University of the Witwatersrand Perinatal HIV Research Unit, Johannesburg, South Africa (Z. Waja, N. Martinson); Weill Cornell Medical College, New York, New York, USA (J.S.V. Mathad); University of California Center for Tuberculosis, San Francisco, California, USA (P. Nahid, P.P.J. Phillips); University of Nebraska Medical Center, Omaha, Nebraska, USA (S. Swindells); Johns Hopkins University School of Medicine, Baltimore, Maryland, USA (R.E. Chaisson); Medical University of South Carolina, Charleston, South Carolina, USA (S.E. Dorman)

Main Article

Table 2

Duration of study drug exposure during pregnancy and pregnancy and infant outcomes in the TB treatment-shortening trial, Tuberculosis Trials Consortium Study 31/AIDS Clinical Trials Group A5349, January 2016–July 2020*

Drug exposure and outcome Pregnancies with exposure to study drugs, N = 30
 Pregnancies without exposure to study drugs, N = 72
Control, n = 13 RPT/MOX, n = 9 RPT, n = 8 Total, N = 30 Control, n = 24 RPT/MOX, n = 26 RPT, n = 22 Total, N = 72
Total no. study drug doses received, median (range)
 157 (27–184)
 118 (54–133)
 107 (81–119)
 118 (27–184)
181 (146–195)
 119 (55–121)
 118 (36–131)
 119 (36–195)
Duration of study drug exposure during pregnancy, d, median (range)
 39 (11–103)
 36 (13–119)
 39 (16–114)
 37 (11–119)
NA
 NA
 NA
 NA
Pregnancy outcome
Live birth, no. (%) 7 (53.8) 7 (77.8) 7 (87.5) 21 (70.0) 18 (75.0) 20 (76.9) 16 (72.7) 54 (75.0)
Fetal death, no. (%) 1 (7.7) 0 0 1 (3.3) 1 (4.2) 0 2 (9.1) 3 (4.2)
Spontaneous abortion, no. (%) 2 (15.4) 1 (11.1) 1 (12.5) 4 (13.3) 0 1 (3.8) 2 (9.1) 3 (4.2)
Elective abortion, no. (%) 3 (23.1) 1 (11.1) 0 4 (13.3) 4 (16.7) 4 (15.4) 1 (4.5) 9 (12.5)
Fetal loss by fetal death or spontaneous abortion, no. (%) 3 (23.1) 1 (11.1) 1 (12.5) 5 (16.7) 1 (4.2%) 1 (3.8) 4 (18.2) 6 (8.3)
Unadjusted risk difference† from control in % with fetal loss (95% CI)‡ Referent −12.0 (−43.8 to 27.7) −10.6 (−42.7 to 29.8) Referent −0.4 (−18.4 to 16.7) 14.0 (−5.9 to 35.4)
Unknown, no. (%)
 0
 0
 0
 0
1 (4.2)
 1 (3.8)
 1 (4.5)
 3 (4.2)
Infant outcomes
Congenital anomaly, no. (% of live births) 0/7 (0.0) 0/7 (0.0) 1/7 (14.3) 1/21 (4.8) 0/18 (0.0) 1/20 (5.0) 0/16 (0.0) 1/54 (1.9)
Unadjusted risk difference§ (95% CI)‡ Referent 0 14.3 (−26.0 to 53.3) Referent 5.0 (−13.8 to 24.2) 0

*MOX, moxifloxacin; NA, not applicable; RPT, rifapentine; TB, tuberculosis. †Difference from control in percentage with fetal loss. Exact 95% CI based on a 2-sided score test (21). §Difference from control in percentage of live births with congenital anomaly.

Main Article

References
  1. Sugarman  J, Colvin  C, Moran  AC, Oxlade  O. Tuberculosis in pregnancy: an estimate of the global burden of disease. Lancet Glob Health. 2014;2:e710–6. DOIPubMedGoogle Scholar
  2. Zumla  A, Bates  M, Mwaba  P. The neglected global burden of tuberculosis in pregnancy. Lancet Glob Health. 2014;2:e675–6. DOIPubMedGoogle Scholar
  3. Mathad  JS, Gupta  A. Tuberculosis in pregnant and postpartum women: epidemiology, management, and research gaps. Clin Infect Dis. 2012;55:1532–49. DOIPubMedGoogle Scholar
  4. Jana  N, Barik  S, Arora  N, Singh  AK. Tuberculosis in pregnancy: the challenges for South Asian countries. J Obstet Gynaecol Res. 2012;38:1125–36. DOIPubMedGoogle Scholar
  5. Grange  J, Adhikari  M, Ahmed  Y, Mwaba  P, Dheda  K, Hoelscher  M, et al. Tuberculosis in association with HIV/AIDS emerges as a major nonobstetric cause of maternal mortality in Sub-Saharan Africa. Int J Gynaecol Obstet. 2010;108:181–3. DOIPubMedGoogle Scholar
  6. Ahmed  Y, Mwaba  P, Chintu  C, Grange  JM, Ustianowski  A, Zumla  A. A study of maternal mortality at the University Teaching Hospital, Lusaka, Zambia: the emergence of tuberculosis as a major non-obstetric cause of maternal death. Int J Tuberc Lung Dis. 1999;3:675–80.PubMedGoogle Scholar
  7. Desai  M, Phillips-Howard  PA, Odhiambo  FO, Katana  A, Ouma  P, Hamel  MJ, et al. An analysis of pregnancy-related mortality in the KEMRI/CDC health and demographic surveillance system in western Kenya. PLoS One. 2013;8:e68733. DOIPubMedGoogle Scholar
  8. Pillay  T, Khan  M, Moodley  J, Adhikari  M, Coovadia  H. Perinatal tuberculosis and HIV-1: considerations for resource-limited settings. Lancet Infect Dis. 2004;4:155–65. DOIPubMedGoogle Scholar
  9. Gupta  A, Mathad  JS, Abdel-Rahman  SM, Albano  JD, Botgros  R, Brown  V, et al. Toward earlier inclusion of pregnant and postpartum women in tuberculosis drug trials: consensus statements from an international expert panel. Clin Infect Dis. 2016;62:761–9. DOIPubMedGoogle Scholar
  10. World Health Organization. Treatment of tuberculosis guidelines. 2010 Jul 15 [cited 2025 Aug 18]. https://www.who.int/publications/i/item/9789241547833
  11. Nahid  P, Dorman  SE, Alipanah  N, Barry  PM, Brozek  JL, Cattamanchi  A, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016;63:e147–95. DOIPubMedGoogle Scholar
  12. SMART4TB Consortium; IMPAACT Network; WHO Global Tuberculosis Programme. Tuberculosis and pregnancy: building consensus on inclusion in research. 2024 Feb [cited 2025 Aug 18]. https://tbcenter.jhu.edu/wp-content/uploads/2024/02/SMART4TB-Pregnancy-and-TB-Report.pdf
  13. US Agency for International Development. SMART4TB Consortium. Washington, D.C. community consensus on the earlier inclusion of pregnant women and persons in TB research. 2024 Feb [cited 2025 Aug 18]. https://www.treatmentactiongroup.org/wp-content/uploads/2024/02/pregnancy_consensus_statement_full_final.pdf
  14. Dorman  SE, Nahid  P, Kurbatova  EV, Phillips  PPJ, Bryant  K, Dooley  KE, et al.; AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Tuberculosis Trials Consortium. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N Engl J Med. 2021;384:1705–18. DOIPubMedGoogle Scholar
  15. Carr  W, Kurbatova  E, Starks  A, Goswami  N, Allen  L, Winston  C. Interim guidance: 4-month rifapentine-moxifloxacin regimen for the treatment of drug-susceptible pulmonary tuberculosis—United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:285–9. DOIPubMedGoogle Scholar
  16. World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: treatment: drug-resistant tuberculosis treatment. 2022 [cited 2025 Aug 18]. https://www.who.int/publications/i/item/9789240063129
  17. Dorman  SE, Nahid  P, Kurbatova  EV, Goldberg  SV, Bozeman  L, Burman  WJ, et al.; AIDS Clinical Trials Group and the Tuberculosis Trials Consortium. High-dose rifapentine with or without moxifloxacin for shortening treatment of pulmonary tuberculosis: Study protocol for TBTC study 31/ACTG A5349 phase 3 clinical trial. Contemp Clin Trials. 2020;90:105938. DOIPubMedGoogle Scholar
  18. World Health Organization. Women of reproductive age (15–49 years) population (thousands). 2025 [cited 2025 Aug 18]. https://www.who.int/data/gho/indicator-metadata-registry/imr-details/women-of-reproductive-age-(15-49-years)-population-(thousands)
  19. American College of Obstetricians and Gynecologists Committee. ACOG Committee Opinion No 579: Definition of term pregnancy. Obstet Gynecol. 2013;122:1139–40. DOIPubMedGoogle Scholar
  20. US Department of Health and Human Services; National Institutes of Health. National Cancer Institute. Common terminology criteria for adverse events (CTCAE) version 4.03. 2010 Jun 14 [cited 2025 Aug 18]. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
  21. Agresti  A, Min  Y. On small-sample confidence intervals for parameters in discrete distributions. Biometrics. 2001;57:963–71. DOIPubMedGoogle Scholar
  22. Rossen  LM, Ahrens  KA, Branum  AM. Trends in risk of pregnancy loss among US women, 1990–2011. Paediatr Perinat Epidemiol. 2018;32:19–29. DOIPubMedGoogle Scholar
  23. Hoyert  DL, Mathews  TJ, Menacker  F, Strobino  DM, Guyer  B. Annual summary of vital statistics: 2004. Pediatrics. 2006;117:168–83. DOIPubMedGoogle Scholar
  24. US Food and Drug Administration. Priftin (rifapentine) tablets. Highlights of prescribing information. 1998 [cited 2025 Aug 18]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021024s009lbl.pdf
  25. Holdiness  MR. Teratology of the antituberculosis drugs. Early Hum Dev. 1987;15:61–74. DOIPubMedGoogle Scholar
  26. Moro  RN, Scott  NA, Vernon  A, Tepper  NK, Goldberg  SV, Schwartzman  K, et al. Exposure to latent tuberculosis treatment during pregnancy. The PREVENT TB and the iAdhere trials. Ann Am Thorac Soc. 2018;15:570–80. DOIPubMedGoogle Scholar
  27. Mathad  JS, Savic  R, Britto  P, Jayachandran  P, Wiesner  L, Montepiedra  G, et al. Pharmacokinetics and safety of 3 months of weekly rifapentine and isoniazid for tuberculosis prevention in pregnant women. Clin Infect Dis. 2022;74:1604–13. DOIPubMedGoogle Scholar
  28. ClinicalTrials.gov. Safety and tolerability of 1 month daily (1HP) and 3 Months Weekly (3HP) isoniazid and rifapentine with pharmacokinetics of dolutegravir (DTG) in pregnant people with HIV (DOLPHIN Moms. 2024 Mar 18 [cited 2025 Aug 18]. https://clinicaltrials.gov/study/NCT05122026?term=DOLPHIN-moms&rank=1
  29. Krasula  RW, Pernet  AG. Comparison of organ-specific toxicity of temafloxacin in animals and humans. Am J Med. 1991;91(6A):38S–41S. DOIPubMedGoogle Scholar
  30. Bar-Oz  B, Moretti  ME, Boskovic  R, O’Brien  L, Koren  G. The safety of quinolones—a meta-analysis of pregnancy outcomes. Eur J Obstet Gynecol Reprod Biol. 2009;143:75–8. DOIPubMedGoogle Scholar
  31. Tabarsi  P, Moradi  A, Baghaei  P, Marjani  M, Shamaei  M, Mansouri  N, et al. Standardised second-line treatment of multidrug-resistant tuberculosis during pregnancy. Int J Tuberc Lung Dis. 2011;15:547–50. DOIPubMedGoogle Scholar
  32. Palacios  E, Dallman  R, Muñoz  M, Hurtado  R, Chalco  K, Guerra  D, et al. Drug-resistant tuberculosis and pregnancy: treatment outcomes of 38 cases in Lima, Peru. Clin Infect Dis. 2009;48:1413–9. DOIPubMedGoogle Scholar
  33. Khan  M, Pillay  T, Moodley  J, Ramjee  A, Padayatchi  N. Pregnancies complicated by multidrug-resistant tuberculosis and HIV co-infection in Durban, South Africa. Int J Tuberc Lung Dis. 2007;11:706–8.PubMedGoogle Scholar
  34. Shin  S, Guerra  D, Rich  M, Seung  KJ, Mukherjee  J, Joseph  K, et al. Treatment of multidrug-resistant tuberculosis during pregnancy: a report of 7 cases. Clin Infect Dis. 2003;36:996–1003. DOIPubMedGoogle Scholar
  35. Acar  S, Keskin-Arslan  E, Erol-Coskun  H, Kaya-Temiz  T, Kaplan  YC. Pregnancy outcomes following quinolone and fluoroquinolone exposure during pregnancy: A systematic review and meta-analysis. Reprod Toxicol. 2019;85:65–74. DOIPubMedGoogle Scholar
  36. Gupta  A, Hughes  MD, Garcia-Prats  AJ, McIntire  K, Hesseling  AC. Inclusion of key populations in clinical trials of new antituberculosis treatments: Current barriers and recommendations for pregnant and lactating women, children, and HIV-infected persons. PLoS Med. 2019;16:e1002882. DOIPubMedGoogle Scholar

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1Members of this group are listed at the end of this article.

2Members of this group are listed at the end of this article.

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